Canine hemangiosarcoma (HSA) is an incurable tumor of cells that line blood vessels in dogs. Of the approximately 65 million owned dogs in the United States in 2004, between 1.5 and 2.5 million will get this disease and die from it. The disease accounts for about 7% of all canine cancers. Because the disease is extremely indolent, treatment is largely ineffective and microscopic metastases are often present at the time of diagnosis. The tumors at this stage are largely resistant to chemotherapy, and thus standard-of-care (surgery and intensive chemotherapy) provides a median survival of little more than six months (Clifford, C. A., et al. (2000) J. Vet. Intern. Med. 14:479-485; Sorenmo, K., et al. (2000), J. Vet. Intern. Med. 14:395-398; and Sorenmo, K. U., et al. (1993) J. Vet. Intern. Med. 7:370-376). Common primary sites for HSA are spleen and right atrium (visceral), and subcutis. Local infiltration and systemic metastases are the common growth patterns and metastatic sites are wide spread, with lung and liver being the most frequently affected organs (Oksanen, A. (1978) J. Comp. Pathol. 88:585-595; and Brown, N. O., et al., (1985) J. Am. Vet. Med. Assoc. 186:56-58). Morbidity and mortality are usually due to acute internal hemorrhage secondary to tumor rupture. Many dogs die from severe abdominal or thoracic hemorrhage before any treatment can be instituted. Although dogs of any age and breed are susceptible to HSA, it occurs more commonly in dogs beyond middle age, and in breeds such as Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, and Skye Terriers, among others. The estimated lifetime risk of HSA in Golden Retrievers is 1 in 5, illustrating the magnitude of this problem.
There is presently no effective technology for early diagnosis of HSA. The only means available to diagnose the disease (for cavitary tumors such as those that occur in the spleen or heart) are imaging methods such as ultrasound and radiographs. Ultrasound, however, although moderately specific is not sensitive. Radiographs are neither specific nor sensitive. Careful examination of blood smears may suggest the presence of chronic hemorrhage (anemia and thrombocytopenia) and vascular abnormalities (red blood cell fragmentation) that are consistent with HSA; however, the method is neither sensitive or specific to confirm the diagnosis. A biopsy is required for confirmation of imaging results, and even then, distinction between hemangiosarcoma and benign proliferative lesions (hemangioma, hematoma) can be difficult. Skin biopsies where there is no lesion would be of little use to provide early diagnosis for cutaneous hemangiosarcoma. The same is true for splenic, hepatic (liver), or cardiac (heart) tumors, with the added issue that the risk of these procedures in the absence of a visible tumor (on radiographs or ultrasound) is unacceptable.
Human angiosarcomas are similar to canine HSA (see, e.g., Fosmire, S. P., et al (2004) Laboratory Investigation 84:562-572). These tumors are uncommon soft tissue sarcomas that can arise in a variety of locations, such as the liver, spleen, skin breast and endocrine organs (see, e.g., Fedok, F. G., et al. (1999) Am J. Otolaryngol. 20:223-231; Hai, S. A., et al., (2000) J. Natl. Med. Assoc. 92:143-146; and Budd, G. T. (2002) Curr. Oncol. Rep. 4:515-519). Like canine HSA, treatment of human angiosarcomas can be challenging and often is not successful.
Given the severity of canine HSA and human angiosarcomas coupled with the lack of effective treatment options once the tumor has metastasized, it would be useful to have a method for early detection of these two diseases. Early detection would allow for treatment options having a higher chance of successfully treating the tumor.